In bio-research, ecological testing, medical testing, drug testing and bio-weapon and hazards detections there is a need for rapid, simultaneous and real time detection of various agents. Typically the agents are provided in a fluid to a test structure, generally an array of some form in which capturing materials of diverse types capable of binding to one or more of the materials undergoing test and provided in the fluid medium. The binding is a result of an affinity that molecules or bio-molecules have for each other and includes the affinities of DNA, RNA, proteins, small molecules and other molecules. DNA arrays and protein arrays, commonly called DNA or protein chips, are two technologies used for bio-molecule affinity sensing in such fields as genomics and proteomics.
The array of capturing materials is created in a known pattern such that by correlation of the binding response of the capturing material to the fluid born molecules under test, it is possible by detecting the level of binding at each array element to determine what materials under test are present. In one case of DNA or RNA testing, various sequences of the DNA or RNA molecule are affixed to corresponding locations in the array. DNA or RNA in the fluid being tested will tend to bind where the sequences therein strongly match the sequences attached to the various array sites.
Test methods known to date fail to provide high throughput, real time operations or to avoid difficult labeling processes, or to avoid capturing material incompatibility with metal sensor surface, requiring cumbersome linking chemistry that may adversely affect binding properties.
Among the techniques previously used which fail to provide all of these requirements in combination are fluorescent tagging. Fluorescent tagging procedures suffer from a number of problems including the difficulty of tagging and the possibility of tagging altering the binding properties. Moreover tagging procedures are difficult to monitor continuously in real time. Among other techniques surface plasmon resonance is popular. This technique, however, requires the affixation of molecules to a metal surface, particularly gold, which has the above mentioned incompatibility problem. Other techniques include waveguide techniques and acoustic detection techniques. Neither of these accommodates a high throughput, requiring a large number of array elements.
Finally, another known technique, reflectometric interference spectroscopy, suffers from the complication of using multiple fiber probes, which greatly hinders its ability to become high throughput.